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Biomedical subjects

R Malessa

Publications and source records attributed to R Malessa.

29 records · Page 2Linked to original sources

Elevation of intracranial pressure in acute AIDS-related cryptococcal meningitis.

Prior to the AIDS-era, elevation of intracranial pressure was known to be a typical complication of cryptococcal meningitis associated with an increased risk of early death. In AIDS-patients, however, the prevalence and clinical significance of this complication are as yet unclear. We analysed clinical features and courses, CSF findings, serological results and neuroimaging scans in acute cryptococcal meningitis in eight patients with AIDS. Five showed symptoms and signs compatible with raised intracranial pressure, which was life-threatening in one and the most probable cause of death in another. Serial monitoring of intracranial pressure together with repeated CSF analysis revealed that severe intracranial pressure elevation in AIDS related cryptococcal meningitis can occur in spite of effective antimycotic treatment, does not depend on an increased CSF/serum osmolality ratio or CSF overproduction and can be associated with normal cranial computed tomography and magnetic resonance imaging findings. Our data support the hypothesis that CSF reabsorption failure plays the crucial role in the pathophysiological mechanism. External lumbar drainage may be of benefit in selected cases of acute AIDS related cryptococcal meningitis with persisting life threatening elevation in intracranial pressure and normal computed tomogram.

AIDS-Related Opportunistic Infections↗

[Progress in vascular dementia--an overview of vascular dementia from past to new concepts].

This article summarizes various concepts (Binswangers encephalopathy, multiinfarct-dementia, lacunar state, mixed dementia, dementia due to amyloid angiopathy or vasculitis) and classifications (DSM, ICD, ADDTC) on vascular dementia. It reviews historical, clinical, and diagnostic aspects (i.e. neuroradiology, SPECT, PET) as well as therapeutic approaches. The confusing nomenclature on vascular dementia is discussed, considering especially the non-convincing concept of multiinfarct-dementia that often has been misused as a synonym for vascular dementia. Multiinfarct-dementia is now restricted to a syndrome of vascular dementia due to several large vessels strokes. A current definition and classification of vascular dementia as suggested by NINDS-AIREN international workshop is described. It defines criteria consistent with the diagnosis of "possible", "probable" and "definite" vascular dementia based on clinical, radiologic and neuropathologic features. The criteria of "probable" vascular dementia include all the following: 1. the presence of dementia and cerebrovascular disease defined by focal signs on neurologic investigation and evidence of relevant cerebrovascular disease by brain imaging (multiple lacunae, extensive white matter lesions, multiple large-vessels infarcts or a strategically placed infarct) 2. A relationship between dementia and cerebrovascular disease (onset of dementia within 3 months following a recognized stroke; abrupt deterioration, stepwise progression). This classification of vascular dementia emphasises pathogenetic aspects and includes dementia resulting from small- and large-vessels disease as well as hypoperfusion, haemorrhagic dementia and dementia due to still unknown factors. Operational criteria for the frequent Binswangers encephalopathy--a prototype of vascular dementia--are presented. Thereby a basis for further research and discussion in this exciting area should have been formed.

Dementia, Multi-Infarct↗

Foscarnet penetrates the blood-brain barrier: rationale for therapy of cytomegalovirus encephalitis.

Foscarnet (phosphonoformate) is a potent virustatic drug against herpes-like viruses and is widely used in the therapy of cytomegalovirus infections in immunosuppressed patients. To obtain data on its penetration across the blood-brain barrier, we determined concentrations of foscarnet in cerebrospinal fluid and in plasma specimens from 26 patients with human immunodeficiency virus (stages 2 to 6 by Walter Reed Army Institute of Research classification) after a single infusion of 90 mg of foscarnet per kg of body weight and at steady state by electrochemical detection by high-pressure liquid chromatography. Penetration coefficients were correlated with the integrity of the blood-brain barrier. After a single infusion of foscarnet, levels in plasma ranged from 297 to 1,775 micrograms/ml (990 to 5,920 mumol/liter), with a mean of 766 +/- 400 micrograms/ml. Corresponding levels in cerebrospinal fluid were 57 to 225 micrograms/ml (190 to 750 mumol/liter), with a mean of 131 +/- 52 micrograms/ml. The penetration coefficient was 0.05 to 0.72 (mean, 0.23 +/- 0.16). At steady state, mean foscarnet levels in plasma were 464 +/- 219 micrograms/ml (1,553 mumol/liter) and mean levels in cerebrospinal fluid were 308 +/- 155 micrograms/ml (1,023 mumol/liter). The penetration coefficient was 0.66 +/- 0.11. Although penetration coefficients were highly variable after a single administration and at steady state, the concentrations of foscarnet attained in cerebrospinal fluid are sufficient for complete inhibition of cytomegalovirus replication in vitro. In conclusion, we show that foscarnet seems to be the drug of choice for the treatment of cytomegalovirus encephalitis, because it penetrates the blood-brain barrier and is found in the cerebrospinal fluid in virustatic concentrations. Foscarnet might be considered for additive therapy for human immunodeficiency virus encephalitis in combination with zidovudine or dideoxyinosine.

AIDS-Related Opportunistic Infections↗

Foscarnet treatment in various cytomegalovirus infections.

We examined the effect of foscarnet (Foscavir) in 15 AIDS patients with cytomegalovirus infection. Cytomegalovirus infection was presented as retinits (n = 8), colitis (n = 3), oral (n = 1) and perianal ulcers (n = 3) and pneumonitis (n = 1). Induction therapy with foscarnet showed a complete response in 9 and a partial response in 6 patients after a medium therapy of 3.5 weeks. Three patients showed progressive disease under ganciclovir and were treated subsequently with foscarnet. Main side effects were ulcers of the glans penis (n = 6) and a rise of creatinine (> 1.5 mg/dl; n = 4). Therapy was changed to ganciclovir because of renal toxicity in 1 patient receiving induction therapy with foscarnet. Within a period of foscarnet therapy between 5 and 9 months (median: 7 months) no clinical progression occurred. Medium survival after diagnosis of cytomegalovirus infection was 7.4 months. We describe our experience with foscarnet and compare treatment results of cytomegalovirus infection at certain locations.

Acquired Immunodeficiency Syndrome↗

[Evoked potentials in neurologically asymptomatic persons during the early stages of HIV infection].

There are few reports on the relevance of evoked potentials in neurologically asymptomatic HIV seropositives. We studied 31 HIV infected males without AIDS or associated clinical neurological abnormalities. Visual evoked potentials by foveal checkerboard stimulation revealed a prolonged VEP latency in 37% of them. HIV seropositives with a pathologic VEP latency showed a significant reduction of their absolute numbers of peripheral blood T-helper cells. This increase of the mean VEP-latency was already significant in HIV seropositives with a T-helper cell count greater than 400/microliters. In 47% of the HIV seropositives the AEP peak I latency was prolonged in combination with a significant decrease of the AEP interpeak latency I-V suggesting endocochlear lesions at peripheral endings of the acoustic nerve or at the basal hair cells. HIV seropositives with a T-helper cell count less than 400/microliters revealed a significant prolongation of the mean AEP interpeak latency III-V indicating a central conduction defect in HIV-seropositives with an immune deficit. Somatosensory evoked potentials after median and tibial nerve stimulation were within the normal range. Since the VEP P100 latencies were significantly longer in HIV seropositives with a normal AEP peak I compared to those with prolonged AEP peak I latencies we postulate that there are different pathophysiological mechanisms underlying.

Adult↗

[Discordant syringomyelia twins in familial syringomyelia].

A case is reported of a pair of monozygous twins who were discordant for and their syringomyelia, and whose brother also suffered from this disease. On the basis of this extraordinarily rare constellation, the role of heredity and the possible importance of environmental factors in the manifestation of syringomyelia are discussed.

Adult↗

Improved autonomic neurocardial balance in short-term abstinent alcoholics treated with acamprosate.

Standardized investigations on resting heart rate variability (HRV) should provide more information on acamprosate's human pharmacodynamic properties because acamprosate interacts with several neurotransmitter systems which are also involved in maintaining autonomic neurocardiac balance. We performed HRV measurements prospectively in 69 healthy controls and 19 chronic alcoholics to prove the hypotheses that: (1) compared to healthy controls, chronic alcoholics show disturbances in neurocardiac vagal function; and (2) in alcoholics, acamprosate treatment (6-8 days) should further decrease parasympathetic activity if acamprosate interacts with central gamma-aminobutyric acidA receptors in vivo. Cardiovagal dysfunction was initially present in 21% of the alcoholics. After treatment. however, their neurocardiac sympathetic-parasympathetic balance improved significantly.

Acamprosate↗

Sensitivity of carbohydrate-deficient transferrin (CDT) in relation to age and duration of abstinence.

Carbohydrate-deficient transferrin (CDT) serum concentrations were prospectively determined in 162 subjects (alcoholics n=62, controls n=100) using three different methods of detection (IEF, CDTect, Axis%CDT). Repeated testing in alcoholics after 3 and 5 days of abstinence demonstrated a significantly higher sensitivity of CDT in patients above 40 years of age compared to younger patients.

Adult↗

Nerve conduction changes in asymptomatic HIV-1 seropositive individuals in the absence of other risk factors for neuropathy.

The major problem in determining the role of HIV-1 infection in the pathogenesis of peripheral neuropathy is the difficulty in separating possible effects of confounding factors such as other infections, malnutrition, neurotoxic medication, drug abuse and antiretroviral treatment. We therefore selected 28 neurologically asymptomatic HIV-seropositive homosexual men (category A, CDC 1993) without other recognized reasons for peripheral nerve disease and 20 age, sex and height matched healthy controls for a prospective nerve conduction study. Nine (32%) HIV-seropositive patients had single nerve conduction abnormalities and 2 (7%) had at least two abnormalities considered to be indicative of subclinical neuropathy. Even patients with normal CD4 cell counts showed significantly lower mean sural nerve conduction velocities and higher tibial distal motor latencies compared to controls (ANOVA; p < 0.05). There was an overall trend toward more frequent nerve conduction changes in subgroups with abnormal CD4 cell counts, lymphocyte responsiveness or beta 2-microglobulin levels. Using strict selection criteria subclinical nerve conduction changes can be found even in the absence of symptomatic HIV-disease or potential confounding factors suggesting that HIV-1 plays a direct role in the pathogenesis of associated peripheral nervous system disease.

Adult↗